VirulencePub Date : 2024-12-01Epub Date: 2024-01-19DOI: 10.1080/21505594.2023.2301243
Mina Yu, Tianqiao Song, Junjie Yu, Huijuan Cao, Xiayan Pan, Zhongqiang Qi, Yan Du, Wende Liu, Yongfeng Liu
{"title":"UvVelC is important for conidiation and pathogenicity in the rice false smut pathogen <i>Ustilaginoidea virens</i>.","authors":"Mina Yu, Tianqiao Song, Junjie Yu, Huijuan Cao, Xiayan Pan, Zhongqiang Qi, Yan Du, Wende Liu, Yongfeng Liu","doi":"10.1080/21505594.2023.2301243","DOIUrl":"10.1080/21505594.2023.2301243","url":null,"abstract":"<p><p>Rice false smut disease is one of the most significant rice diseases worldwide. <i>Ustilaginoidea virens</i> is the causative agent of this disease. Although several developmental and pathogenic genes have been identified and functionally analyzed, the pathogenic molecular mechanisms of <i>U. virens</i> remain elusive. The velvet family regulatory proteins are involved in fungal development, conidiation, and pathogenicity. In this study, we demonstrated the function of the VelC homolog UvVELC in <i>U. virens</i>. We identified the velvet family protein UvVELC and characterized its functions using a target gene deletion-strategy. Deletion of <i>UvVELC</i> resulted in conidiation failure and pathogenicity. The <i>UvVELC</i> expression levels during infection suggested that this gene might be involved in the early infection process. <i>UvVELC</i> is also important in resistance to abiotic stresses, the utilization efficiency of glucose, stachyose, raffinose, and other sugars, and the expression of transport-related genes. Moreover, UvVELC could physically interact with UvVEA in yeast, and <i>UvVELC</i>/<i>UvVEA</i> double-knockout mutants also failed in conidiation and pathogenicity. These results indicate that <i>UvVELC</i> play a critical role in the conidiation and pathogenicity in <i>U. virens</i>. Functional analysis indicated that UvVELC-mediated conidiation and nutrient acquisition from rice regulates the pathogenicity of <i>U. virens</i>. Understanding the function of the UvVELC homolog could provide a potential molecular target for controlling rice false smut disease.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirulencePub Date : 2024-12-01Epub Date: 2024-02-15DOI: 10.1080/21505594.2024.2313413
Jennie S Campbell, James C Pearce, Attila Bebes, Arnab Pradhan, Raif Yuecel, Alistair J P Brown, James G Wakefield
{"title":"Characterising phagocytes and measuring phagocytosis from live Galleria mellonella larvae.","authors":"Jennie S Campbell, James C Pearce, Attila Bebes, Arnab Pradhan, Raif Yuecel, Alistair J P Brown, James G Wakefield","doi":"10.1080/21505594.2024.2313413","DOIUrl":"10.1080/21505594.2024.2313413","url":null,"abstract":"<p><p>Over the last 20 years, the larva of the greater waxmoth, <i>Galleria mellonella</i>, has rapidly increased in popularity as an <i>in vivo</i> mammalian replacement model organism for the study of human pathogens. Experimental readouts of response to infection are most often limited to observing the melanization cascade and quantifying larval death and, whilst transcriptomic and proteomic approaches, and methods to determine microbial load are also used, a more comprehensive toolkit of profiling infection over time could transform the applicability of this model. As an invertebrate, <i>Galleria</i> harbour an innate immune system comprised of both humoral components and a repertoire of innate immune cells - termed haemocytes. Although information on subtypes of haemocytes exists, there are conflicting reports on their exact number and function. Flow cytometry has previously been used to assay <i>Galleria</i> haemocytes, but protocols include both centrifugation and fixation - physical methods which have the potential to affect haemocyte morphology prior to analysis. Here, we present a method for live haemocyte analysis by flow cytometry, revealing that <i>Galleria</i> haemocytes constitute only a single resolvable population, based on relative size or internal complexity. Using fluorescent zymosan particles, we extend our method to show that up to 80% of the <i>Galleria</i> haemocyte population display phagocytic capability. Finally, we demonstrate that the developed assay reliably replicates <i>in vitro</i> data, showing that cell wall β-1,3-glucan masking by <i>Candida albicans</i> subverts phagocytic responses. As such, our method provides a new tool with which to rapidly assess phagocytosis and understand live infection dynamics in <i>Galleria</i>.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirulencePub Date : 2024-12-01Epub Date: 2024-03-05DOI: 10.1080/21505594.2024.2322961
Yixuan Xi, Xinru Li, Lu Liu, Feichen Xiu, Xinchao Yi, Hongliang Chen, Xiaoxing You
{"title":"Sneaky tactics: Ingenious immune evasion mechanisms of <i>Bartonella</i>.","authors":"Yixuan Xi, Xinru Li, Lu Liu, Feichen Xiu, Xinchao Yi, Hongliang Chen, Xiaoxing You","doi":"10.1080/21505594.2024.2322961","DOIUrl":"10.1080/21505594.2024.2322961","url":null,"abstract":"<p><p>Gram-negative <i>Bartonella</i> species are facultative intracellular bacteria that can survive in the harsh intracellular milieu of host cells. They have evolved strategies to evade detection and degradation by the host immune system, which ensures their proliferation in the host. Following infection, <i>Bartonella</i> alters the initial immunogenic surface-exposed proteins to evade immune recognition via antigen or phase variation. The diverse lipopolysaccharide structures of certain <i>Bartonella</i> species allow them to escape recognition by the host pattern recognition receptors. Additionally, the survival of mature erythrocytes and their resistance to lysosomal fusion further complicate the immune clearance of this species. Certain <i>Bartonella</i> species also evade immune attacks by producing biofilms and anti-inflammatory cytokines and decreasing endothelial cell apoptosis. Overall, these factors create a challenging landscape for the host immune system to rapidly and effectively eradicate the <i>Bartonella</i> species, thereby facilitating the persistence of <i>Bartonella</i> infections and creating a substantial obstacle for therapeutic interventions. This review focuses on the effects of three human-specific <i>Bartonella</i> species, particularly their mechanisms of host invasion and immune escape, to gain new perspectives in the development of effective diagnostic tools, prophylactic measures, and treatment options for <i>Bartonella</i> infections.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FlyPub Date : 2024-12-01Epub Date: 2024-05-13DOI: 10.1080/19336934.2024.2352938
Nicole A Losurdo, Adriana Bibo, Jacob Bedke, Nichole Link
{"title":"A novel <i>adipose</i> loss-of-function mutant in <i>Drosophila</i>.","authors":"Nicole A Losurdo, Adriana Bibo, Jacob Bedke, Nichole Link","doi":"10.1080/19336934.2024.2352938","DOIUrl":"10.1080/19336934.2024.2352938","url":null,"abstract":"<p><p>To identify genes required for brain growth, we took an RNAi knockdown reverse genetic approach in <i>Drosophila</i>. One potential candidate isolated from this effort is the anti-lipogenic gene <i>adipose</i> (<i>adp</i>). Adp has an established role in the negative regulation of lipogenesis in the fat body of the fly and adipose tissue in mammals. While fat is key to proper development in general, <i>adp</i> has not been investigated during brain development. Here, we found that RNAi knockdown of <i>adp</i> in neuronal stem cells and neurons results in reduced brain lobe volume and sought to replicate this with a mutant fly. We generated a novel <i>adp</i> mutant that acts as a loss-of-function mutant based on buoyancy assay results. We found that despite a change in fat content in the body overall and a decrease in the number of larger (>5 µm) brain lipid droplets, there was no change in the brain lobe volume of mutant larvae. Overall, our work describes a novel <i>adp</i> mutant that can functionally replace the long-standing <i>adp</i><sup><i>60</i></sup> mutant and shows that the <i>adp</i> gene has no obvious involvement in brain growth.</p>","PeriodicalId":12128,"journal":{"name":"Fly","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-06-20DOI: 10.1080/15592294.2024.2368995
Luís Teves, Ana Rosa Vieira Melo, Ana F Ferreira, Mafalda Raposo, Carolina Lemos, Conceição Bettencourt, Manuela Lima
{"title":"Global DNA methylation is not elevated in blood samples from Machado-Joseph disease mutation carriers.","authors":"Luís Teves, Ana Rosa Vieira Melo, Ana F Ferreira, Mafalda Raposo, Carolina Lemos, Conceição Bettencourt, Manuela Lima","doi":"10.1080/15592294.2024.2368995","DOIUrl":"10.1080/15592294.2024.2368995","url":null,"abstract":"<p><p>Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia (SCA) caused by a polyglutamine expansion in the ataxin-3 protein, which initiates a cascade of pathogenic events, including transcriptional dysregulation. Genotype-phenotype correlations in MJD are incomplete, suggesting an influence of additional factors, such as epigenetic modifications, underlying the MJD pathogenesis. DNA methylation is known to impact the pathophysiology of neurodegenerative disorders through gene expression regulation and increased methylation has been reported for other SCAs. In this work we aimed to analyse global methylation in MJD carriers. Global 5-mC levels were quantified in blood samples of 33 MJD mutation carriers (patients and preclinical subjects) and 33 healthy controls, matched by age, sex, and smoking status. For a subset of 16 MJD subjects, a pilot follow-up analysis with two time points was also conducted. No differences were found in median global 5-mC levels between MJD mutation carriers and controls and no correlations between methylation levels and clinical or genetic variables were detected. Also, no alterations in global 5-mC levels were observed over time. Our findings do not support an increase in global blood methylation levels associated with MJD.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirulencePub Date : 2024-12-01Epub Date: 2024-07-29DOI: 10.1080/21505594.2024.2384563
Chuan-Min Zhou, Ze-Zheng Jiang, Ning Liu, Xue-Jie Yu
{"title":"Current insights into human pathogenic phenuiviruses and the host immune system.","authors":"Chuan-Min Zhou, Ze-Zheng Jiang, Ning Liu, Xue-Jie Yu","doi":"10.1080/21505594.2024.2384563","DOIUrl":"10.1080/21505594.2024.2384563","url":null,"abstract":"<p><p>Phenuiviruses are a class of segmented negative-sense single-stranded RNA viruses, typically consisting of three RNA segments that encode four distinct proteins. The emergence of pathogenic phenuivirus strains, such as Rift Valley fever phlebovirus (RVFV) in sub-Saharan Africa, Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in East and Southeast Asia, and Heartland Virus (HRTV) in the United States has presented considerable challenges to global public health in recent years. The innate immune system plays a crucial role as the initial defense mechanism of the host against invading pathogens. In addition to continued research aimed at elucidating the epidemiological characteristics of phenuivirus, significant advancements have been made in investigating its viral virulence factors (glycoprotein, non-structural protein, and nucleoprotein) and potential host-pathogen interactions. Specifically, efforts have focused on understanding mechanisms of viral immune evasion, viral assembly and egress, and host immune networks involving immune cells, programmed cell death, inflammation, nucleic acid receptors, etc. Furthermore, a plethora of technological advancements, including metagenomics, metabolomics, single-cell transcriptomics, proteomics, gene editing, monoclonal antibodies, and vaccines, have been utilized to further our understanding of phenuivirus pathogenesis and host immune responses. Hence, this review aims to provide a comprehensive overview of the current understanding of the mechanisms of host recognition, viral immune evasion, and potential therapeutic approaches during human pathogenic phenuivirus infections focusing particularly on RVFV and SFTSV.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirulencePub Date : 2024-12-01Epub Date: 2024-05-07DOI: 10.1080/21505594.2024.2348252
Kuan Feng, Benjamin Bendiwhobel Ushie, Haiyan Zhang, Shu Li, Fei Deng, Hualin Wang, Yun-Jia Ning
{"title":"Pathogenesis and virulence of Heartland virus.","authors":"Kuan Feng, Benjamin Bendiwhobel Ushie, Haiyan Zhang, Shu Li, Fei Deng, Hualin Wang, Yun-Jia Ning","doi":"10.1080/21505594.2024.2348252","DOIUrl":"10.1080/21505594.2024.2348252","url":null,"abstract":"<p><p>Heartland virus (HRTV), an emerging tick-borne pathogenic bunyavirus, has been a concern since 2012, with an increasing incidence, expanding geographical distribution, and high pathogenicity in the United States. Infection from HRTV results in fever, thrombocytopenia, and leucopenia in humans, and in some cases, symptoms can progress to severe outcomes, including haemorrhagic disease, multi-organ failure, and even death. Currently, no vaccines or antiviral drugs are available for treatment of the HRTV disease. Moreover, little is known about HRTV-host interactions, viral replication mechanisms, pathogenesis and virulence, further hampering the development of vaccines and antiviral interventions. Here, we aimed to provide a brief review of HRTV epidemiology, molecular biology, pathogenesis and virulence on the basis of published article data to better understand this virus and provide clues for further study.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirulencePub Date : 2024-12-01Epub Date: 2024-09-06DOI: 10.1080/21505594.2024.2395837
Dongchang He, Xiyue Wang, Huiguang Wu, Kairui Cai, Xiaoli Song, Xiaoquan Wang, Jiao Hu, Shunlin Hu, Xiaowen Liu, Chan Ding, Daxin Peng, Shuo Su, Min Gu, Xiufan Liu
{"title":"Characterization of Conserved Evolution in H7N9 Avian Influenza Virus Prior Mass Vaccination.","authors":"Dongchang He, Xiyue Wang, Huiguang Wu, Kairui Cai, Xiaoli Song, Xiaoquan Wang, Jiao Hu, Shunlin Hu, Xiaowen Liu, Chan Ding, Daxin Peng, Shuo Su, Min Gu, Xiufan Liu","doi":"10.1080/21505594.2024.2395837","DOIUrl":"10.1080/21505594.2024.2395837","url":null,"abstract":"<p><p>Vaccination is crucial for the prevention and mitigation of avian influenza infections in China. The inactivated H7N9 vaccine, when administered to poultry, significantly lowers the risk of infection among both poultry and humans, while also markedly decreasing the prevalence of H7N9 detections. Highly pathogenic (HP) H7N9 viruses occasionally appear, whereas their low pathogenicity (LP) counterparts have been scarcely detected since 2018. However, these contributing factors remain poorly understood. We conducted an exploratory investigation of the mechanics via the application of comprehensive bioinformatic approaches. We delineated the Yangtze River Delta (YRD) H7N9 lineage into 5 clades (YRD-A to E). Our findings highlight the emergence and peak occurrence of the LP H7N9-containing YRD-E clade during the 5th epidemic wave in China's primary poultry farming areas. A more effective control of LP H7N9 through vaccination was observed compared to that of its HP H7N9 counterpart. YRD-E exhibited a tardy evolutionary trajectory, denoted by the conservation of its genetic and antigenic variation. Our analysis of YRD-E revealed only minimal amino acid substitutions along its phylogenetic tree and a few selective sweep mutations since 2016. In terms of epidemic fitness, the YRD-E was measured to be lower than that of the HP variants. Collectively, these findings underscore the conserved evolutionary patterns distinguishing the YRD-E. Given the conservation presented in its evolutionary patterns, the YRD-E LP H7N9 is hypothesized to be associated with a reduction following the mass vaccination in a relatively short period owing to its lower probability of antigenic variation that might affect vaccine efficiency.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirulencePub Date : 2024-12-01Epub Date: 2024-09-24DOI: 10.1080/21505594.2024.2399792
Kris Gerard Alvarez, Lisa Goral, Abdulhadi Suwandi, Lisa Lasswitz, Francisco J Zapatero-Belinchón, Katrin Ehrhardt, Kumar Nagarathinam, Katrin Künnemann, Thomas Krey, Agnes Wiedemann, Gisa Gerold, Guntram A Grassl
{"title":"Human tetraspanin CD81 facilitates invasion of <i>Salmonella enterica</i> into human epithelial cells.","authors":"Kris Gerard Alvarez, Lisa Goral, Abdulhadi Suwandi, Lisa Lasswitz, Francisco J Zapatero-Belinchón, Katrin Ehrhardt, Kumar Nagarathinam, Katrin Künnemann, Thomas Krey, Agnes Wiedemann, Gisa Gerold, Guntram A Grassl","doi":"10.1080/21505594.2024.2399792","DOIUrl":"10.1080/21505594.2024.2399792","url":null,"abstract":"<p><p>Human CD81 and CD9 are members of the tetraspanin family of proteins characterized by a canonical structure of four transmembrane domains and two extracellular loop domains. Tetraspanins are known as molecular facilitators, which assemble and organize cell surface receptors and partner molecules forming clusters known as tetraspanin-enriched microdomains. They have been implicated to play various biological roles including an involvement in infections with microbial pathogens. Here, we demonstrate an important role of CD81 for the invasion of epithelial cells by <i>Salmonella enterica</i>. We show that the overexpression of CD81 in HepG2 cells enhances invasion of various typhoidal and non-typhoidal <i>Salmonella</i> serovars. Deletion of CD81 by CRISPR/Cas9 in intestinal epithelial cells (C2BBe1 and HT29-MTX-E12) reduces <i>S</i>. Typhimurium invasion. In addition, the effect of human CD81 is species-specific as only human but not rat CD81 facilitates <i>Salmonella</i> invasion. Finally, immunofluorescence microscopy and proximity ligation assay revealed that both human tetraspanins CD81 and CD9 are recruited to the entry site of <i>S</i>. Typhimurium during invasion but not during adhesion to the host cell surface. Overall, we demonstrate that the human tetraspanin CD81 facilitates <i>Salmonella</i> invasion into epithelial host cells.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-01-03DOI: 10.1080/15592294.2023.2298057
Allan Andersen, Emily Milefchik, Emma Papworth, Brandan Penaluna, Kelsey Dawes, Joanna Moody, Gracie Weeks, Ellyse Froehlich, Kaitlyn deBlois, Jeffrey D Long, Robert Philibert
{"title":"<i>ZSCAN25</i> methylation predicts seizures and severe alcohol withdrawal syndrome.","authors":"Allan Andersen, Emily Milefchik, Emma Papworth, Brandan Penaluna, Kelsey Dawes, Joanna Moody, Gracie Weeks, Ellyse Froehlich, Kaitlyn deBlois, Jeffrey D Long, Robert Philibert","doi":"10.1080/15592294.2023.2298057","DOIUrl":"10.1080/15592294.2023.2298057","url":null,"abstract":"<p><p>Currently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to hospitals for consideration of withdrawal syndrome (AWS). However, only a fraction of those admitted will experience severe AWS. Previously, we and others have shown that epigenetic indices, such as the Alcohol T-Score (ATS), can quantify recent alcohol consumption. However, whether these or other alcohol biomarkers, such as carbohydrate deficient transferrin (CDT), could identify those at risk for severe AWS is unknown. To determine this, we first conducted genome-wide DNA methylation analyses of subjects entering and exiting alcohol treatment to identify loci whose methylation quickly reverted as a function of abstinence. We then tested whether methylation at a rapidly reverting locus, cg07375256, or other existing metrics including PAWSS scores, CDT levels, or ATS, could predict outcome in 125 subjects admitted for consideration of AWS. We found that PAWSS did not significantly predict severe AWS nor seizures. However, methylation at cg07375256 (<i>ZSCAN25</i>) and CDT strongly predicted severe AWS with ATS (<i>p</i> < 0.007) and cg07375256 (<i>p</i> < 6 × 10-5) methylation also predicting AWS associated seizures. We conclude that epigenetic methods can predict those likely to experience severe AWS and that the use of these or similar Precision Epigenetic approaches could better guide AWS management.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10766392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}